The studies described are designed to provide clues to the mechanism by which human polymorphonuclear neutrophils (PMN) and monocytes sense and migrate directionally in response to a chemical gradient. These studies will employ a new method developed by the applicant for measurement of human leukocyte migration and chemotaxis which involves migration under agarose gel. A multiple approach is planned in which both morphological and biochemical aspects of spontaneous migration and chemotaxis will be studied using both PMN and monocytes from both healthy donors and patients with various infectious and neoplastic diseases. Morphological studies will include examination of migrating cells by scanning and transmission electron microscopy. Biochemical studies will include experiments dealing with the influence of cytotoxins on spontaneous migration, directional migration, enzyme activation, lysosomal enzyme release and superoxide production. These studies will provide information on the roles of microtubules and microfilaments in leukocyte migration, the homology of receptors for different cytotoxins on cells of one type, and the relationship of enzyme activation and enzyme and superoxide release to chemotaxis.